Project Summary

Chong-Bin Zhu, M.D., Ph.D. (Young Investigator 2005) of Vanderbilt University Medical Center, plans to study the role of immune factors on the regulation of the serotonin transporter (SERT), which is the primary target for antidepressants, and abnormalities in which may contribute to psychiatric disorders. Recent studies demonstrate that compromised immune function, induced by environmental stresses and inflammatory mediators, may trigger, modulate or sustain mental illness, including depression and schizophrenia. But the connection between immune factors and psychiatric diseases remains elusive. Dr. Zhu, however, recently has found that p38 mitogen-activated protein kinase (38MAPK)--which is activated by cytokines and environmental and chemical stressors—plays a crucial role in the regulation of SERT. Preliminary studies show that p38 MAPK activators stimulate serotonin transport, and activated p38 MAPK phosphorylates purified SERT protein. Dr. Zhu hypothesizes that p38 MAPK modulates SERT activity via phosphorylation, possibly by catalytically activating the SERT protein. The goal of this proposal is to elucidate the role of p38 MAPK and relevant inflammatory cytokines in SERT phosphorylation and activation, by examining the effects of cytokines on SERT activity in cell lines and neuronal preparations. These studies should elucidate the role of neuroimmune processes in SERT regulation and may provide new insight into the relationship between environmentally sensitive inflammatory cytokines and serotonin-modulated psychiatric disorders.

Program Area: MOOD DISORDERS

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